rs6066029

Positions:

• chr20-46588889-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000279027.9(SLC13A3):​c.1016+271G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,160 control chromosomes in the GnomAD database, including 1,460 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1460 hom., cov: 32)
• Consequence: SLC13A3 ENST00000279027.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602

Genes affected

SLC13A3 (HGNC:14430): (solute carrier family 13 member 3) Mammalian sodium-dicarboxylate cotransporters transport succinate and other Krebs cycle intermediates. They fall into 2 categories based on their substrate affinity: low affinity and high affinity. Both the low- and high-affinity transporters play an important role in the handling of citrate by the kidneys. The protein encoded by this gene represents the high-affinity form. Alternatively spliced transcript variants encoding different isoforms have been found for this gene, although the full-length nature of some of them have not been characterized yet. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC13A3	NM_022829.6	c.1016+271G>A		intron_variant		ENST00000279027.9	NP_073740.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC13A3	ENST00000279027.9	c.1016+271G>A		intron_variant		1	NM_022829.6	ENSP00000279027	P1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19231 AN: 152042 Hom.: 1453 Cov.: 32

Gnomad AFR AF: 0.0868

Gnomad AMI AF: 0.0738

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.0862

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.0843

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.116

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.127 AC: 19257 AN: 152160 Hom.: 1460 Cov.: 32 AF XY: 0.130 AC XY: 9692 AN XY: 74394

Gnomad4 AFR AF: 0.0869

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.0862

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.0835

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.122

Alfa AF: 0.118 Hom.: 172

Bravo AF: 0.131

Asia WGS AF: 0.215 AC: 746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.8
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6066029; hg19: chr20-45217528;